Interestingly, mutations in the same conserved residue of PIEZO2 (mPIEZO2; R2756; hPIEZO2 R2686) are associated with distal arthrogryposis, Gordon syndrome and the Marden-Walker syndrome, all of which are human developmental disorders.15,16 Here we show that each of these single mutations can abrogate the voltage-block of the PIEZO2 channel, dramatically increasing channel availability at physiological membrane potentials. Here, PIEZO2 is linked to distal arthrogryposis.